Neonatal clonidine treatment results in long-lasting changes in noradrenaline sensitivity and kindling epileptogenesis.
In the present experiment we tested the hypothesis that early interference with noradrenaline transmission can have permanent consequences for brain function in adulthood. Neonatal depletion of noradrenaline by daily subcutaneous injections of clonidine results in supersensitivity to noradrenaline in adult hippocampal CA1 cells as shown in our previous microiontophoretic study. These findings were confirmed and extended here with dose-response curves. Furthermore, we tested whether this form of neonatal interference with noradrenaline also permanently affects long-lasting plasticity as revealed in kindling epileptogenesis in adulthood. The initiation of the epileptic activity after the kindling stimulation was significantly delayed in the clonidine-treated group, and all measured parameters of seizure expression tended to be retarded in comparison with saline-treated control rats. This indicates that noradrenaline supersensitivity induced by neonatal clonidine treatment retards kindling development in adulthood.
Gorter
J A
JA
Netherlands Institute for Brain Research, Amsterdam, The Netherlands.
Kamphuis
W
W
Huisman
E
E
Bos
N P
NP
Mirmiran
M
M
D000818:Animals; D000831:Animals, Newborn; D003000:Clonidine / Q000494:pharmacology*; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D007478:Iontophoresis; D007696:Kindling, Neurologic / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000502:physiology; D013997:Time Factors
D003000:Clonidine; D009638:Norepinephrine